The comparison revealed significant changes in DNA methylation associated with CVID, specifically the hypermethylation of several genes of relevance in B-cell biology, including PIK3CD, BCL2L1, RPS6KB2, TCF3 and KCNN4. The comparison of the DNA methylation status of selected genes from the above screening in naive, unswitched and switched memory B cells from a cohort of healthy versus CVID individuals revealed that the aforementioned hypermethylation does not affect the naive cell subpopulation. This evidence concerns the gene RPS6KB2 and common variable immunodeficiency.